Similarities in physiological effects observed with lower aliphatic N-(2-chloroethyl)-N-nitroso carbamates and mustard gas have been the background for investigations of such carbamates as antitumor agents. The results reported are summarized in Table 1 and show that the compounds investigated are highly toxic and have no activities against any of the tumors against which they have been examined.
Table 1 ______________________________________ Toxicity and lack of antitumor activity reported for N-chloroethyl-N-nitroso carbamates. - ClCH.sub.2 CH.sub.2 N-- COOR .vertline. NO R LD50 mg/kg.sup. a) ______________________________________ C.sub.2 H.sub.5 -- 2.sup.b) (CH.sub.3).sub.2 CHCH.sub.2 -- 7.sup.c) CH.sub.3 (CH.sub.2).sub.2 CH.sub.2 -- 11 - 15.sup.d) Phenyl 3 - 7.sup.d) .beta.-Naphthyl 42.sup.d) ______________________________________ .sup.a) Acute intraperitoneal toxicity in mice. .sup.b) Reported by K. A. Hyde et al. in J. Med. and Pharm. Chem. 5 (1962 1. This compound was found to be inactive against the tumors investigated lymphoid leukemia (L 1210), Sarcoma 180 and Adenocarcinoma 755. .sup.c) Reported by W. C. J. Ross in J. Med. Chem. 10 (1967) 108. This compound was found to be inactive against the tumors investigated: Walker 256 and lymphoid leukemia (L 1210). .sup.d) Reported by S. P. Kramer et al. in Cancer 12 (1959) 446.
It has now, surprisingly, been found that N-halogenoalkyl-N-nitroso carbamates of steroid compounds have a low toxicity and also are highly active against animal tumors. It has also been found that N.sup.4 -halogenoalkyl-N.sup.4 -nitroso allophanates of steroid compounds have the same valuable properties.
Depending on the nature of steroid, these compounds also show such pharmacological activities which derive from the steroids themselves, e.g., estrogenic, androgenic, anabolic, gestogenic, and corticoid activities. As many steroids are used in connection with treatment of cancer diseases, the steroid part of the molecule can be selected with relation to the kind of tumor which is to be treated.
It is well-known that the effect of steroids can be changed, e.g. prolonged, by esterification and etherification of suitable hydroxy groups in their molecules and also steroids can be made water soluble in the form of salts of acid esters of such hydroxy groups. When the N-halogenoalkyl-N-nitroso carbamates and N.sup.4 -halogenoalkyl-N.sup.4 -nitroso allophanates of a steroid according to the invention have one or more remaining free hydroxy groups suitable for esterifications and etherifications, such hydroxy groups can therefore also be present in the compounds of the invention in the form of inorganic or organic esters and organic ethers thereby to confer upon the N-halogenoalkyl-N-nitroso carbamates and N.sup.4 -halogenoalkyl-N.sub.4 -nitroso allophanates of such steroids such properties as mentioned above.